tbuckley/cabot-search huggingface dataset:
Oncological outcomes of sentinel lymph node procedure-based radiotherapy versus imaging-based radiotherapy for clinically localized prostate cancer – a multicenter, retrospective, propensity score weighted comparison
Authors: H.A. De Barros, N. Grivas, J.J. Duin, D. Mulder, V. Van Der Noort, M.A. Noordzij, E.M.K. Wit, E.E. Schaake, P.J. Van Leeuwen, H.G. Van Der Poel
Journal: European Urology (2022)
LGG-20. Defining subgroups in low grade gliomas by their immune and stromal microenvironment
Authors: Meik Körner, Michael Spohn, Ulrich Schüller, Michael Bockmayr
Journal: Neuro-Oncology (2022)

Abstract Immunologic treatment options are still uncommon in low grade gliomas, although such therapies might be beneficial for inoperable and aggressive cases. Knowledge on immune and stromal cells in low grade gliomas, which is a mandatory prerequisite for such approaches, is still scarce. We therefore gathered published gene-expression data from 400 low grade gliomas as well as 302 high grade gliomas in order to quantify 10 microenvironment cell populations. First, we investigated general differences in the microenvironment of low- and high-grade gliomas. Lower-grade and high-grade tumors cluster together, respectively, and show a general similarity within and distinct differences between these groups, the main difference being a higher infiltration of fibroblasts and T-cells in high-grade gliomas. Among the analysed entities, gangliogliomas and pleomorphic xanthoastrocytomas presented the highest overall immune cell infiltration. Further analyses of the low-grade gliomas presented three distinct microenvironmental signatures of immune cell infiltration, which can be divided into T-cell/dendritic/natural killer cell-, neutrophilic/B lineage/natural killer cell-, and monocytic/vascular/stromal-dominated immune clusters. These clusters correlated with tumor location, age, and histological diagnosis, but not with sex or progression-free survival. Our work shows that low- and high-grade gliomas can be characterized and differentiated by their immune cell infiltration. Low grade gliomas cluster into three distinct immunologic tumor microenvironments, which may be of further interest for upcoming immunotherapeutic research.
Changes in Cancer Screening in the US During the COVID-19 Pandemic
Authors: Stacey A. Fedewa, Jessica Star, Priti Bandi, Adair Minihan, Xuesong Han, K. Robin Yabroff, Ahmedin Jemal
Journal: JAMA Network Open (2022)

Health care was disrupted in the US during the first quarter of 2020 with the emergence of the COVID-19 pandemic. Early reports in selected samples suggested that cancer screening services decreased greatly, but population-based estimates of cancer screening prevalence during 2020 have not yet been reported.To examine changes in breast cancer (BC), cervical cancer (CC), and colorectal cancer (CRC) screening prevalence with contemporary national, population-based Behavioral Risk Factor Surveillance System (BRFSS) data.This survey study included respondents from the 2014, 2016, 2018, and 2020 BRFSS surveys who were eligible for BC (women aged 50-74 years), CC (women aged 25-64 years), and CRC (women and men aged 50-75 years) screening. Data analysis was performed from September 2021 to February 2022.Calendar year.Self-reported receipt of a recent (defined as in the past year) BC, CC, and CRC screening test. Adjusted prevalence ratios (aPRs) comparing 2020 vs 2018 prevalence and 95% CIs were computed.In total, 479 248 individuals were included in the analyses of BC screening, 301 453 individuals were included in CC screening, and 854 210 individuals were included in CRC screening, In 2020, among respondents aged 50 to 75 years, 14 815 (11.4%) were Black, 12 081 (12.6%) were Hispanic, 156 198 (67.3%) were White, and 79 234 (29.9%) graduated from college (all percentages are weighted). After 4 years (2014-2018) of nearly steady prevalence, past-year BC screening decreased by 6% between 2018 and 2020 (from 61.6% in 2018 to 57.8% in 2020; aPR, 0.94; 95% CI, 0.92-0.96), and CC screening decreased by 11% (from 58.3% in 2018 to 51.9% in 2020; aPR, 0.89; 95% CI, 0.87-0.91). The magnitude of these decreases was greater in people with lower educational attainment and Hispanic persons. CRC screening prevalence remained steady; past-year stool testing increased by 7% (aPR, 1.07; 95% CI, 1.02-1.12), offsetting a 16% decrease in colonoscopy (aPR, 0.84; 95% CI, 0.82-0.88) between 2018 and 2020.In this survey study, stool testing increased and counterbalanced a decrease in colonoscopy during 2020, and BC and CC screening modestly decreased. How these findings might be associated with outcomes is not yet known, but they will be important to monitor, especially in populations with lower socioeconomic status, who experienced greater screening decreases during the COVID-19 pandemic.
Micromanaging atherosclerosis: myeloid cell-specific microRNA-26b attenuates atherosclerosis development
Authors: L Peters, K Bidzhekov, Y Jansen, S Bayasgalan, S Gencer, SS Sundararaman, A Bonnin-Marquez, Y Yan, AM Jans, M Bartneck, Y Doering, C Weber, E Van Der Vorst
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: None. Increasing evidence has shown that microRNAs (miRs) are fundamental players in atherosclerosis, but the exact role of various miRs remains elusive. Preliminary data showed that, with a 5-fold increase, miR-26b was the most highly expressed miR in human atherosclerotic plaques compared to healthy vessels. Therefore, we aimed to determine its cell-specific effects on atherosclerosis development. We examined the role of miR-26b in atherosclerosis by using full-body knockout (KO) mice on a 4 weeks and 12 weeks Western type diet (WTD) and myeloid cell-specific miR-26b KO (LysM-Cre) mice on 12 weeks WTD on an apolipoprotein E-deficient background. Atherosclerotic plaque size and phenotype were analyzed via immunohistochemical and immunofluorescent stainings. The phenotype and function of bone marrow-derived macrophages (BMDMs) from full body KO mice were analyzed via PCR, ELISA and gelatinase assays. Lipid nanoparticles (LNPs) served as vehicles for miR-26b mimics to restore miR-26b levels in knockout BMDMs. A full-body miR-26b-KO on a 12 weeks WTD resulted in a striking 3.5-fold increase in atherosclerotic lesion size, compared to control. Consistent with a more advanced plaque phenotype, collagen content, smooth muscle cell percentage and relative necrotic core area were all significantly increased in plaques from miR-26b KO mice whilst the relative macrophage content was significantly reduced. Interestingly, the full-body KO mice on a 4 weeks WTD showed a remarkable 10-fold increase in plaque size and the respective plaques also had a reduced macrophage percentage, showing that miR-26b has very strong effects on both atherogenesis as well as atherosclerosis progression. Intriguingly, relative plaque size in the arches of miR-26b LysM-Cre mice were increased by 3-fold and collagen content was also increased significantly, suggesting a role for myeloid-specific miR-26b in atherosclerosis development. Further highlighting its myeloid-specific effects, miR-26b KO BMDMs showed an increase in IL-6 and TNFα secretion, which could be rescued by LNPs containing miR-26b mimics. Additionally, these miR-26b KO BMDMs showed a reduction in collagen breakdown. Overall, our results clearly demonstrate an atheroprotective role of myeloid cell-specific miR-26b by attenuating lesion initiation as well as progression, mainly by suppressing inflammation and stimulating collagen breakdown. Our study leads to exciting new insights into the role of miR-26b in atherosclerosis development, providing an important back-bone for future research and potential new treatment options.
Perverse Incentives — HIV Prevention and the 340B Drug Pricing Program
Authors: Julia L. Marcus, Amy Killelea, Douglas S. Krakower
Journal: New England Journal of Medicine (2022)

A decade after preexposure prophylaxis against HIV became available, less than a quarter of people in the United States who could benefit from PrEP are taking it. The failure is, in part, a perverse outcome of a system that relies on high drug prices to fund HIV prevention.
Assessment of tissue and blood tumor mutational burden in patients with melanoma using a 523-gene clinical assay.
Authors: Tindaro Giardina, Timothy Humphries, Anna Reid, Nima MesbahArdakani, Cleo Robinson, Michael Millward, Elin Gray, Benhur Amanuel
Journal: Journal of Clinical Oncology (2022)

e21570 Background: High tumor mutation burden (TMB) predicts improved efficacy of immune checkpoint inhibitors (ICIs) across a range of malignancies, including melanoma. Circulating tumor DNA (ctDNA) has emerged as a powerful complement to tumor biopsies for the diagnosis and clinical management of cancer patients. The TruSight Oncology 500 (TSO500) clinical assay interrogates 523 cancer-related genes and has shown good concordance between tissue and ctDNA using a high throughput sequencer such as NovaSeq. There are no studies looking at concordance and utility of this assay using more affordable mid throughput platforms. Here we present a pilot study comparing TSO500 sequencing results from matched tumor and plasma specimens and concordance of selected actionable gene variants investigated by ctDNA digital PCR. Methods: Samples from 18 metastatic cutaneous melanoma patients with matched formalin-fixed, paraffin-embedded (FFPE) tumor tissue and plasma collected in Streck tubes had DNA extracted for library preparation using the Illumina TSO500 NGS assay with inputs of ≥40ng of FFPE DNA and ≥10ng of ctDNA. Libraries were sequenced on a NextSeq2000 P3 flow cell to achieve recommended sequencing depth of 800 million reads per sample. A TMB cut off ≥10 mut/Mb was used as high TMB. Droplet digital PCR (ddPCR) was performed for orthogonal validation of selected clinically significant somatic mutations. Results: Sequencing on the NextSeq2000 achieved an average of 797 million pass filter reads per sample and somatic variant allele frequency (VAF) sensitivity down to 0.12%, which exceeded vendor recommendations. There was 75% concordance on the TMB classification (low and high values, Cohen’s k = 0.714) based on tumor and plasma (r = 0.86, p &lt; 0.01) on 8 paired samples (extended analysis will be presented). Some high TMB cases carried POLE or POLD1 variants. Actionable variants identified by ctTSO500 in 15 cases were confirmed by ddPCR, with an outstanding concordance of their VAF (R 2 = 0.99, p &lt; 0.0001). Diagnosis of tier I/II actionable variants (21 variants; 81% accuracy) was achieved in 7 matched tumor tissue and blood samples. Some variants found in tumor tissue were not detected in the blood. Conclusions: This pilot study demonstrates the clinical utility of the TSO500 ctDNA panel using an affordable mid throughput sequencing platform to identify actionable variants and TMB from blood specimens with high sensitivity and specificity. Testing of a larger cohort of matched tumor and plasma samples will serve to evaluate the clinical utility of the TSO500 ctDNA panel as a complement or alternative strategy to tissue biopsy for the genomic profiling of melanoma patients.
Cost-effectiveness of Implementing Smoking Cessation Interventions for Patients With Cancer
Authors: Douglas E. Levy, Susan Regan, Giselle K. Perez, Alona Muzikansky, Emily R. Friedman, Julia Rabin, Nancy A. Rigotti, Jamie S. Ostroff, Elyse R. Park
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Guidelines recommend cancer care clinicians offer smoking cessation treatment. Cost analyses will help stakeholders understand and plan for implementation of cessation programs. <h3>Objective</h3> To estimate the incremental cost per quit (ICQ) of adopting an intensive smoking cessation intervention among patients undergoing treatment at cancer care clinics, from a clinic perspective. <h3>Design, Setting, and Participants</h3> This economic evaluation, a secondary analysis of the Smokefree Support Study (conducted 2013-2018; completed 2021), used microcosting methods and sensitivity analyses to estimate the ICQ of the interventions. Participants included patients undergoing treatment for a broad range of solid tumors and lymphomas who reported current smoking and were receiving care at cancer care clinics within 2 academic medical centers. <h3>Exposures</h3> Intensive smoking cessation treatment (up to 11 counseling sessions with free medications), standard of care (up to 4 counseling sessions with medication advice), or usual care (referral to the state quitline). <h3>Main Outcomes and Measures</h3> Total costs, component-specific costs, and the ICQ of the intensive smoking cessation treatment relative to both standard of care (comparator in the parent randomized trial) and usual care (a common comparator outside this trial) were calculated. Overall and post hoc site-specific estimates are provided. Because usual care was not included in the parent trial, sensitivity analyses were conducted to assess how assumptions about usual care quit rates affected study outcomes (ie, base case [from a published smoking cessation trial among patients with thoracic cancer], best case, and conservative case scenarios). <h3>Results</h3> The per-patient costs of offering intensive smoking cessation treatment, standard of care, and usual care were $1989, $1482, and $0, respectively. For intensive treatment, the dominant costs were treatment (35%), staff supervision (26%), and patient enrollment (24%). Relative to standard of care, intensive treatment had an overall ICQ of $3906, and one site had an ICQ of $2892. Relative to usual care, intensive treatment had an ICQ of $9866 overall (base case), although at one site, the ICQ was $5408 (base case) and $3786 (best case). <h3>Conclusions and Relevance</h3> In this economic evaluation study, implementation of an intensive smoking cessation treatment intervention was moderately to highly cost-effective, depending on existing smoking cessation services in place.
Association of metabolic risk factors with breast cancer survival in a population-based cohort.
Authors: Elizabeth Feliciano, Alexa Zimbalist, Bette Jane Caan, Elizabeth A. Mittendorf, Deborah Dillon, Charles P. Quesenberry, Wendy Y. Chen
Journal: Journal of Clinical Oncology (2022)

12089 Background: Metabolic abnormalities may impact breast cancer prognosis, but research has been limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In a population based cohort, we utilized time-updated laboratory values and adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides) and breast cancer survival. Methods: 13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL, LDL, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Lab values were updated a median of 5 times between 1-7 years post-diagnosis. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, and diabetes, and then for dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, and tamoxifen v. aromatase inhibitors). Results: Mean (SD) age at diagnosis was 62.3 (11.8) years. Over median follow-up of 9 years, 2,876 patients died (1,080 of breast cancer). Patients with low HDL (≤45 vs. &gt;45 mg/dL) had higher breast cancer-specific mortality (HR, 1.87; 95% CI, 1.62-2.16); high levels of glucose, triglycerides, and LDL were not associated. The increased risk associated with low HDL persisted after adjusting for tumor characteristics, cancer treatment, and medications. Conclusions: Low HDL evaluated over time after cancer diagnosis is associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Cholesterol may play a role in breast cancer due to its role in cell membrane structure, signaling pathways, and steroid hormone synthesis. Future studies should address whether pharmacologic or lifestyle treatment of lipids after breast cancer diagnosis can optimize survival outcomes.[Table: see text]
Association Between Walking for Exercise and Symptomatic and Structural Progression in Individuals With Knee Osteoarthritis: Data From the Osteoarthritis Initiative Cohort
Authors: Grace H. Lo, Surabhi Vinod, Michael J. Richard, Matthew S. Harkey, Timothy E. McAlindon, Andrea M. Kriska, Bonny Rockette‐Wagner, Charles B. Eaton, Marc C. Hochberg, Rebecca D. Jackson, C. Kent Kwoh, Michael C. Nevitt, Jeffrey B. Driban
Journal: Arthritis & Rheumatology (2022)

To assess the relationship between walking for exercise and symptomatic and structural disease progression in individuals with knee osteoarthritis (OA).We assessed a nested cohort of participants age 50 years or older within the Osteoarthritis Initiative, a community-based observational study in which subjects were enrolled between 2004 and 2006. We focused on 4 dichotomous outcomes from baseline to the 48-month visit, involving determination of the frequency of knee pain and radiographic severity of knee OA on posteroanterior semiflexed knee radiographs. The outcomes assessed included 1) new frequent knee pain, 2) worsening of radiographic severity of knee OA based on the Kellgren/Lawrence grade, 3) progression of medial joint space narrowing, and 4) improved frequent knee pain. We used a modified version of the Historical Physical Activity Survey Instrument to ascertain those subjects who reported walking for exercise after age 50 years. The survey was administered at the 96-month visit (2012-2014).Of 1,212 participants with knee OA, 45% were male and 73% reported walking for exercise. The mean ± SD age was 63.2 ± 7.9 years, and the mean ± SD body mass index was 29.4 ± 4.6 kg/m2 . The likelihood of new frequent knee pain was reduced in participants with knee OA who walked for exercise as compared to those who were non-walkers (odds ratio [OR] 0.6, 95% confidence interval [95% CI] 0.4-0.8), and progression of medial joint space narrowing was less common in walkers compared to non-walkers (OR 0.8, 95% CI 0.6-1.0).In individuals with knee OA who were age 50 years or older, walking for exercise was associated with less frequent development of knee pain. These findings support the notion that walking for exercise should be encouraged for people with knee OA. Furthermore, we offer a proof of concept that walking for exercise could be disease modifying, which warrants further study.
PEP503 (NBTXR3), a radioenhancer, in combination with concurrent chemoradiation (CCRT) in locally advanced or recurrent head and neck squamous cell carcinoma (HNSCC): Dose-finding of a phase 1b/2 trial.
Authors: Cheng-Hsu Wang, K.S.Clifford Chao, Ping-Tsung Chen, Kun-Yun Yeh, Yen-Chao Chen, Yao-Liang Chen, Shih-Wei Yang, Tsung-Han Wu, Pei-Hung Chang, Chi-Kuang Young, Din-Li Tsan, Ming-Hsui Tsai, Ching-Yun Hsieh, Wen-Cheng Chen, Yuan-Hsiung Tsai, Cheng-Ming Hsu, John W. C. Chang, Wei-Che Yu, Bor-Nian Shen
Journal: Journal of Clinical Oncology (2022)

e18041 Background: PEP503 (aka NBTXR3), a novel radioenhancer composed of functionalized hafnium oxide nanoparticles, is designed for intratumoral injection to increase radiation energy deposition within solid tumors and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. PEP503 nanoparticles plus RT has been tested in elderly HNSCC patients and has demonstrated a good safety profile. The phase 1b part of the study aimed to test the feasibility and the recommended phase 2 dose (RP2D) of PEP503 intratumoral injection when added with low-dose (LD) weekly cisplatin-containing chemoradiation (CCRT) in HNSCC. Methods: Patients who had T3-4 locally advanced HNSCC suitable for CCRT were eligible. An intratumoral single injection of PEP503 was performed 24 to 72 hours before the start of CCRT: consisting of IMRT (70̃72 Gy, 2-2.12 Gy/fraction) and weekly cisplatin (low dose, 40 mg/m 2 ) concurrently during IMRT. Traditional 3+3 design was planned for dose escalation and 5 levels of PEP503 were planned, including 5%, 10%, 15%, 22%, and 33% of the baseline GTV by MRI. PEP503 Intra-tumor dispersion was anayzed by CT-scan. Results: Twelve (12) patients (male/female: 11/1; oral cavity/oropharynx: 11/1) were enrolled, with 3, 6, and 3 patients at 5%, 10%, and 15% PEP503 dose levels, respectively, in combination with LD cisplatin CCRT. DLTs were observed in one patient at 10% dose level which were G3 ALT and G3 AST increased. Common G3 AEs observed across dose levels were stomatitis (50.0%), WBC decreased (33.3%), decreased appetite (16.7%), neutrophil count decreased (16.7%), and leukopenia (16.7%), and only one G4 AE (hyponatraemia) was observed. CT images demonstrated PEP503 within the tumor contour after injection throughout the CCRT period. Hafnium, for all patients, was either not detected or below the Lower Limit of Quantification (LLOQ) in the circulation 60 minutes after PEP503 intratumoral injection, and not found in urine. DCR was achieved in 100% of patients with responding patients for an ORR of 58.3%. No subjects received salvage surgery after study treatment. Study was terminated early before MTD and RP2D could be determined. Conclusions: Adding PEP503, a radioenhancer, via a single intratumoral injection to weekly cisplatin-containing CCRT was feasible and safe for patients with locally advanced or recurrent LA-HNSCC. RP2D was not reached due to study early termination. Clinical trial information: NCT02901483.